1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment

Kouwenhoven, Mathilde C.M.; Kros, Johan M.; French, Pim J.; Stege, Elize M. Biemond-ter; Graveland, Wilfried J.; Taphoorn, Martin J.B.; Brandes, Alba A.; Bent, Martin J. van den

doi:10.1016/j.ejca.2006.05.021

Cited by 109 publications

(49 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Importantly, we did not only detect frequent 5 0 -CpGisland hypermethylation and reduced expression of PRDX1 in oligodendroglial tumours with 1p and 19q deletions but also provided first evidence that this aberration may be linked to radio-and chemosensitivity of Hs683 glioma cells in vitro. Clinically, it has been well documented in numerous retrospective and prospective studies that 1p/19q deletion in low-grade and anaplastic oligodendroglial tumours predicts response to radiotherapy as well as chemotherapy with TMZ or nitrosourea compounds (Brada et al, 2003;Cairncross et al, 2006;Kouwenhoven et al, 2006;van den Bent, 2006;Wick et al, 2009). The molecular basis for the predictive power of 1p/19q deletion is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

View full text Add to dashboard Cite

Deletions of chromosomal arms 1p and 19q are frequent in oligodendroglial tumours and linked to radio-and chemotherapy response as well as longer survival. The molecular mechanisms underlying this clinically important association are as yet unknown. Here, we studied the peroxiredoxin 1 (PRDX1) gene at 1p34.1 for promoter methylation and expression in primary gliomas and investigated its role in radio-and chemosensitivity of glioma cells in vitro. In total, we screened primary glioma tissues from 93 patients for methylation of the 5 0 -CpG island of PRDX1 by sodium bisulfite sequencing. PRDX1 mRNA and protein expression levels were determined in subsets of the tumours by quantitative PCR and western blot analysis, respectively. PRDX1 hypermethylation and reduced expression were frequently detected in oligodendroglial tumours and secondary glioblastomas, but not in primary glioblastomas. In oligodendroglial tumours, both PRDX1 hypermethylation and reduced mRNA expression were significantly associated with 1p/19q-deletion. Stable knockdown of PRDX1 by lentiviral transduction of shorthairpin (sh)RNA constructs significantly increased apoptosis and reduced cell viability of Hs683 glioma cells exposed to ionizing irradiation or temozolomide in vitro. Taken together, our findings indicate that epigenetic silencing of PRDX1 is frequent in 1p/19q-deleted oligodendroglial tumours and likely contributes to radioand chemosensitivity of these tumours.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The current study applies the same immunohistochemical method to silent subtype 3 adenomas in an effort to determine their possible susceptibility to temozolomide treatment. Its utility in the treatment of various tumors, specifically gliomas of oligodendroglial type and some pituitary adenomas, is well established [12,13].…”

Section: Introductionmentioning

confidence: 99%

MGMT Immunoexpression in Silent Subtype 3 Pituitary Adenomas: Possible Therapeutic Implications

et al. 2010

View full text Add to dashboard Cite

The objective of the study was to assess O(6)-methylguanine-DNA methyltransferase (MGMT) immunoreactivity in pituitary adenomas of silent subtype 3 as a potential indicator of temozolomide susceptibility. The Mayo Clinic Anatomic Pathology Database was searched for all cases of silent subtype 3 pituitary adenoma. Each of the 23 cases identified had been confirmed on the basis of histology, immunohistochemical staining for pituitary hormones, as well as on diagnostic ultrastructural criteria. Unstained microscopic sections were immunostained for MGMT and were semiquantitatively assessed. Of the 23 tumors examined, 18 (78%) showed no MGMT immunoreactivity. The remaining five (22%) showed immunoreactivity in < or =50% of tumor cells. Among eight of the most clinically aggressive tumors in this study, six (75%) lacked MGMT immunoreactivity. The observed lack of or low-level expression of MGMT by this distinctive, clinically aggressive form of pituitary adenoma suggests potential efficacy of treatment with the alkylating agent temozolomide.

show abstract

“…The majority of patients in our study had prognostically favorable prognostic factors such as oligodendroglial histology, complete resection, age below 50 years and positive molecular outcome markers, particularly 1p/19q deletion, IDH1 mutation and MGMT promoter methylation [23,[30][31][32]. However, a complete resection proved to be the only relevant factor for PFS in our statistical analysis.…”

Section: Discussionmentioning

confidence: 61%

Temozolomide and 13-cis retinoic acid in patients with anaplastic gliomas: a prospective single-arm monocentric phase-II study (RNOP-05)

et al. 2011

View full text Add to dashboard Cite

The objective of this prospective, monocentric phase-II pilot study was to evaluate toxicity and efficacy of neoadjuvant temozolomide (TMZ) and 13-cis retinoic acid (13-cRA) treatment in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection. The primary endpoint of the study was median progression-free survival (PFS). Secondary endpoints were toxicity and PFS rates at 6, 12 and 24 months. Thirty-two adult patients were included in the study and treated with a median number of 10 TMZ and 13-cRA cycles (range 1-26). The majority of patients had favorable prognostic factors characterized by young age, complete resection, oligodendroglial histology, 1p/19q co-deletion, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation and isocitrate dehydrogenase 1 (IDH1) mutation. Grade 3/4 myelotoxicity occurred in 5/32 patients, and about 90% of patients suffered from grade 2/3 adverse events attributable to 13-cRA. The median PFS was 37.8 months (95% CI 22.2-53.4). The 6-, 12- and 24-month PFS rates were 84.4, 75 and 42.4%. The extent of tumor resection was the only prognostic factor associated with better PFS. TMZ and 13-cRA treatment did not improve PFS when retrospectively compared to the TMZ-treated group within the randomized NOA-04 phase-III trial. In conclusion, 13-cRA addition to TMZ in a neoadjuvant setting showed acceptable toxicity, but did not yield an advantage in PFS in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection.

show abstract

1p/19q loss within oligodendroglioma is predictive for response to first line temozolomide but not to salvage treatment

Cited by 109 publications

References 19 publications

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

MGMT Immunoexpression in Silent Subtype 3 Pituitary Adenomas: Possible Therapeutic Implications

Temozolomide and 13-cis retinoic acid in patients with anaplastic gliomas: a prospective single-arm monocentric phase-II study (RNOP-05)

Contact Info

Product

Resources

About